Association between maternal plasma one-carbon biomarkers during pregnancy and fetal growth in twin pregnancies / 中华妇产科杂志

Objective: To characterize the relationship between the levels of plasma methyl donor and related metabolites (including choline, betaine, methionine, dimethylglycine and homocysteine) and fetal growth in twin pregnancies. Methods: A hospital-based cohort study was used to collect clinical data of 92 pregnant women with twin pregnancies and their fetuses who were admitted to Peking University Third Hospital from March 2017 to January 2018. Fasting blood was collected from the pregnant women with twin pregnancies (median gestational age: 18.9 weeks). The levels of methyl donors and related metabolites in plasma were quantitatively analyzed by high-performance liquid chromatography combined with mass spectrometry. The generalized estimation equation was used to analyze the relationship between maternal plasma methyl donors and related metabolites levels and neonatal outcomes of twins, and the generalized additive mixed model was used to analyze the relationship between maternal plasma methyl donors and related metabolites levels and fetal growth ultrasound indicators. Results: (1) General clinical data: of the 92 women with twin pregnancies, 66 cases (72%) were dichorionic diamniotic (DCDA) twin pregnancies, and 26 cases (28%) were monochorionic diamniotic (MCDA) twin pregnancies. The comparison of the levels of five plasma methyl donors and related metabolites in twin pregnancies with different basic characteristics showed that the median levels of plasma choline and betaine in pregnant women ≥35 years old were higher than those in pregnant women <35 years old, and the differences were statistically significant (all P<0.05). (2) Correlation between plasma methyl donor and related metabolites levels and neonatal growth indicators: after adjusting for confounding factors, plasma homocysteine level in pregnant women with twins was significantly negatively correlated with neonatal birth weight (β=-47.9, 95%CI:-94.3- -1.6; P=0.043). Elevated methionine level was significantly associated with decreased risks of small for gestational age infants (SGA; OR=0.5, 95%CI: 0.3-0.9; P=0.021) and low birth weight infants (OR=0.6, 95%CI: 0.4-0.9; P=0.020). Increased homocysteine level was associated with increased risks of SGA (OR=1.5, 95%CI: 1.0-2.2; P=0.029) and inconsistent growth in twin fetuses (OR=1.9, 95%CI: 1.0-3.7; P=0.049). (3) Correlation between the levels of plasma methyl donors and related metabolites and intrauterine growth indicators of twins pregnancies: for every 1 standard deviation increase in plasma choline level in pregnant women with twin pregnancies, fetal head circumference, abdominal circumference, femoral length and estimated fetal weight in the second trimester increased by 1.9 mm, 2.6 mm, 0.5 mm and 20.1 g, respectively, and biparietal diameter, abdominal circumference and estimated fetal weight increased by 0.7 mm, 3.0 mm and 38.4 g in the third trimester, respectively, and the differences were statistically significant (all P<0.05). (4) Relationship between plasma methyl donor and related metabolites levels in pregnant women with different chorionicity and neonatal birth weight and length: the negative correlation between plasma homocysteine level and neonatal birth weight was mainly found in DCDA twin pregnancy (β=-65.9, 95%CI:-110.6- -21.1; P=0.004). The levels of choline, betaine and dimethylglycine in plasma of MCDA twin pregnancy were significantly correlated with the birth weight and length of newborns (all P<0.05). Conclusion: Homocysteine level is associated with low birth weight in twins, methionine is associated with decreased risk of SGA, and choline is associated with fetal growth in the second and third trimesters of pregnancy.

Targeting Peripheral μ-opioid Receptors or μ-opioid Receptor-Expressing Neurons Does not Prevent Morphine-induced Mechanical Allodynia and Anti-allodynic Tolerance / 神经科学通报·英文版

The chronic use of morphine and other opioids is associated with opioid-induced hypersensitivity (OIH) and analgesic tolerance. Among the different forms of OIH and tolerance, the opioid receptors and cell types mediating opioid-induced mechanical allodynia and anti-allodynic tolerance remain unresolved. Here we demonstrated that the loss of peripheral μ-opioid receptors (MORs) or MOR-expressing neurons attenuated thermal tolerance, but did not affect the expression and maintenance of morphine-induced mechanical allodynia and anti-allodynic tolerance. To confirm this result, we made dorsal root ganglia-dorsal roots-sagittal spinal cord slice preparations and recorded low-threshold Aβ-fiber stimulation-evoked inputs and outputs in superficial dorsal horn neurons. Consistent with the behavioral results, peripheral MOR loss did not prevent the opening of Aβ mechanical allodynia pathways in the spinal dorsal horn. Therefore, the peripheral MOR signaling pathway may not be an optimal target for preventing mechanical OIH and analgesic tolerance. Future studies should focus more on central mechanisms.

Recent Progress of Palbociclib in Treatment of HR+/HER2- Breast Cancer / 肿瘤防治研究

As the first cyclin-dependent kinases 4 and 6 inhibitors, palbociclib significantly improved the survival of the patients with the hormone receptor-positive and human epidermal growth factor receptor-2 negative breast cancer. Palbociclib is a crucial landmark in the development history of antineoplastic drugs. This article reviews the mechanism of palbociclib, and summarizes the clinical trials, side effects, and the application of palbociclib.

Research on the lipid-lowering effect of traditional Chinese medicine using lipidomics technology / 药学学报

Hyperlipidemia is a common disease with abnormal blood lipids and is an important risk factor for various cardiovascular diseases. Traditional Chinese medicine has the advantages of dependable lipid-lowering effects with few side effects and is widely used in the prevention and treatment of hyperlipidemia in China. However, due to the complex composition of traditional Chinese medicine and the many targets for treating hyperlipidemia, the mechanisms by which these medicines lower lipid levels are not well resolved. Lipidomics is a discipline that studies lipids and the interaction of lipids in biological systems. Lipidomics can identify and quantify the lipids in vivo under physiological and pathological conditions, helping to discover the potential biomarkers related to the lipid-lowering effects of traditional Chinese medicine and providing a basis for systematically studying the lipid-lowering effect of traditional Chinese medicine. This review introduces the principal research methods used in lipidomics and summarizes the results and prospects of application of lipidomics in the research on the lipid-lowering effects of traditional Chinese medicine.

A nomogram model based on cone beam CT radiomics combined with clinical features and dosimetric parameters predicting radiation pneumonitis in patients with esophageal cancer receiving radiotherapy / 中华放射肿瘤学杂志

Objective:To develop and validate a nomogram model for predicting radiation-induced pneumonitis in esophageal cancer based on CBCT radiomics characteristics combined with clinical characteristics and lung dosimetric parameters.Methods:Clinical data, dosimetric parameters and CBCT images of 96 patients with thoracic middle esophageal squamous cell carcinoma treated by intensity-modulated radiation therapy (IMRT) from 2017 to 2019 were analyzed retrospectively. The CBCT images of each patient in three different time periods were obtained. All patients were assigned randomly into the primary cohort ( n=67) and validation cohort ( n=29). Double lungs were selected as the region of interest (ROI), and 3D-slicer software was used for image segmentation and feature extraction. The LASSO regression were applied to identify candidate radiomic features and construct the Rad-score. The optimal time period, clinical and dosimetric parameters were selected to construct the nomogram model, and then the area under the receiver operating characteristic curve (AUC) was used to evaluate the prediction effect of the model. Results:The predictive capacity of the model in the first time period was the highest. In the primary cohort, the AUC was 0.700(95% CI: 0.568-0.832), the sensitivity was 61.5%, and the specificity was 75.0%. In the validation cohort, the AUC was 0.765(95% CI: 0.588-0.941), the sensitivity was 84.6% and the specificity was 64.7%, respectively. In the combined nomogram model, the AUC in the primary cohort was 0.836(95% CI: 0.700-0.918), the sensitivity was 96.0% and the specificity was 54.8%. In the validation cohort, the AUC was 0.905(95% CI: 0.799-1.000), the sensitivity was 92.9% and the specificity was 73.3%, respectively. The diagnostic efficiency of combined nomogram model was the best. Conclusions:The nomogram model based on early lung CBCT radiomics has certain predictive efficiency for RP. The model of lung CBCT radiomics in early stage of radiotherapy can predict RP of esophageal cancer. The nomogram model based on Rad-score combined with V 5Gy, MLD and tumor stage yields better predictive accuracy, which can be used as a quantitative prediction model for RP.

The anti-glioma effects of borneol and RGD co-modified docetaxel loaded nanoparticles after intranasal administration / 药学学报

Borneol (Bo) and Arg-Gly-Asp (RGD) co-modified docetaxel (DTX) loaded MPEG-PLGA nanoparticles (DTX-Bo-RGD-NPs) were prepared to improve the therapeutic effect of DTX against glioma after intranasal administration. DTX-Bo-RGD-NPs were prepared by emulsification-solvent evaporation method, and their morphology, particle size, zeta potential, drug loading capacity (DLC), stability, and in vitro release properties were investigated. The fluorescence probe coumarin-6 loaded NPs were prepared for investigating the NPs' uptake property on C6 and 16HBE cell models to evaluate in vitro targeting ability. The DiR loaded NPs were prepared for observing the fluorescence intensity at the brain tumor site after intranasal administration through in vivo imaging system in a C6 rat orthotropic model, evaluating the targeting ability in vivo. The anti-tumor effects of DTX-Bo-RGD-NPs were also investigated in such C6 rat orthotropic model in vivo. Animal welfare and experimental procedures are in compliance with the regulations of the Animal Ethics Committee of Shanghai University of Traditional Chinese Medicine. The results showed that DTX-Bo-RGD-NPs were spherical and uniformly distributed, with a particle size of about 140 nm and a zeta potential of -20 to -30 mV. The drug delivery system showed good stability and sustained release property in vitro, and favorable brain tumor targeting effect in vitro and in vivo. Such novel drug delivery system significantly improved the accumulation of DTX-Bo-RGD-NPs in tumor sites and displayed a higher brain tumor targeting efficiency, providing promising therapeutics of DTX for the treatment of glioma after intranasal administration.

Crotalaria ferruginea extract attenuates lipopolysaccharide-induced acute lung injury in mice by inhibiting MAPK/NF-κB signaling pathways

Objective: To evaluate the anti-inflammatory activity of Crotalaria ferruginea extract (CFE) and its mechanism. Methods: An intratracheal lipopolysaccharide (LPS) instillation-induced acute lung injury (ALI) model was used to study the anti-inflammatory activity of CFE in vivo. The LPS-induced shock model was used to analyze the effect of CFE on survival. LPS-stimulated RAW264.7 cell model was used to investigate the anti-inflammatory activity of CFE in vitro and the effects on mitogen-Activated protein kinase (MAPK) or nuclear factor-κB (NF-κB) signaling pathways. Results: CFE administration decreased the number of inflammatory cells, reduced the levels of tumor necrosis factor-α (TNF-A), monocyte chemotactic protein-1 (MCP-1), interleukin-6 (IL-6), and interferon-γ, and diminished protein content in the bronchoalveolar lavage fluid of mice. CFE also reduced lung wet-To-dry weight ratio, myeloperoxidase, and lung tissue pathological injury. CFE pre-Administration improved the survival rate of mice challenged with a lethal dose of LPS. CFE reduced LPS-Activated RAW264.7 cells to produce nitric oxide, TNF-α, MCP-1, and IL-6. Furthermore, CFE inhibited nuclear translocation and phosphorylation of NF-κB P65, extracellular signal-regulated kinase, c-Jun N-Terminal kinases, and P38 MAPKs. Conclusions: CFE exhibits potent anti-inflammatory activity in LPS-induced ALI mice, LPS-shock mice, and RAW264.7 cells, and its mechanism may be associated with the inhibition of NF-κB and MAPK signaling pathways. Crotalaria ferruginea may be a useful therapeutic drug for the treatment of ALI and other respiratory inflammations.

Crotalaria ferruginea extract attenuates lipopolysaccharide-induced acute lung injury in mice by inhibiting MAPK/NF-κB signaling pathways

Objective: To evaluate the anti-inflammatory activity of Crotalaria ferruginea extract (CFE) and its mechanism. Methods: An intratracheal lipopolysaccharide (LPS) instillation-induced acute lung injury (ALI) model was used to study the anti-inflammatory activity of CFE in vivo. The LPS-induced shock model was used to analyze the effect of CFE on survival. LPS-stimulated RAW264.7 cell model was used to investigate the anti-inflammatory activity of CFE in vitro and the effects on mitogen-Activated protein kinase (MAPK) or nuclear factor-κB (NF-κB) signaling pathways. Results: CFE administration decreased the number of inflammatory cells, reduced the levels of tumor necrosis factor-α (TNF-A), monocyte chemotactic protein-1 (MCP-1), interleukin-6 (IL-6), and interferon-γ, and diminished protein content in the bronchoalveolar lavage fluid of mice. CFE also reduced lung wet-To-dry weight ratio, myeloperoxidase, and lung tissue pathological injury. CFE pre-Administration improved the survival rate of mice challenged with a lethal dose of LPS. CFE reduced LPS-Activated RAW264.7 cells to produce nitric oxide, TNF-α, MCP-1, and IL-6. Furthermore, CFE inhibited nuclear translocation and phosphorylation of NF-κB P65, extracellular signal-regulated kinase, c-Jun N-Terminal kinases, and P38 MAPKs. Conclusions: CFE exhibits potent anti-inflammatory activity in LPS-induced ALI mice, LPS-shock mice, and RAW264.7 cells, and its mechanism may be associated with the inhibition of NF-κB and MAPK signaling pathways. Crotalaria ferruginea may be a useful therapeutic drug for the treatment of ALI and other respiratory inflammations.

Analysis of related factors of radiation pneumonitis after radiotherapy for thoracic segment esophageal cancer / 中华放射医学与防护杂志

Objective:To investigate the effects of clinical characteristics, irradiation techniques and dose-volume parameters on radiation pneumonitis(RP) in thoracic segment esophageal cancer patients, so as to provide reference for the formulation of radiotherapy protocol for thoracic esophageal cancer.Methods:The incidence of RP in 247 patients with thoracic segment esophageal cancer from June 2014 to June 2019 was analyzed retrospectively, then univariate and multivariate analyses were performed on the clinical characteristics, radiation techniques and lung dosimetry parameters of these patients. The area under receiver operating characteristic (ROC) curve was used to verify the diagnostic efficacy of RP≥grade 1, ≥grade 2 and ≥grade 3.Results:There were 118 cases (47.8%)with RP≥grade 1, 54 cases (21.9%)with RP≥grade 2, 17 cases (6.9%)with RP≥grade 3. The result of univariate analysis showed that lung V5- V40 and MLD were both related to the occurrence of RP≥grade 1( Z=-5.802 to -4.306, P<0.05). ≥grade 2, and≥grade 3, respectively( F=0.057 to 11.616、0.087 to 3.392, P<0.05). GTV volume, PTV volume, GTV/lung volume(%) and PTV/lung volume(%) were related to RP≥grade 1( Z=-3.377 to -2.041, P<0.05)and RP≥grade 2( F=3.600 to 9.801, P<0.05). Smoking index >400 was significantly correlated with RP≥grade 3( χ2=13.295, P<0.05), and chronic obstructive pulmonary disease (COPD) was significantly correlated with RP≥grade 1( χ2=9.146, P<0.05). However, there was no significant correlation between RP and different irradiation techniques, chemotherapy factors, radiotherapy dose, esophageal cancer stage and cancer location.The result of multivariate analysis showed that V5 and V40 were independent risk factors of RP≥grade 1(AUC 55.74%、4.13%)、MLD was independent risk factors of RP≥grade 2 (AUC 11.91 Gy), and V5 was independent risk factors of RP≥grade 3(AUC 57.60%). The smoking index>400 was the independent risk factor of RP≥grade 3 ( Wald=5.964, P<0.05), and COPD was the independent risk factor of RP≥1 grade ( Wald=6.110, P<0.05). Conclusions:The incidence of RP is low after radiotherapy for thoracic segment esophageal cancer. The dosimetric parameters such as lung V5, V40, MLD, smoking degree, COPD and other clinical characteristics are closely related to the occurrence of RP of corresponding grades.

Strategy for the identification and quantitative analysis of the phytochemicals of traditional Chinese medicine by LC-MS/MS / 药学学报

Traditional Chinese medicine (TCM) has made numerous contributions to the prosperity of China. However, the phytochemicals of TCM are complex, and there are significant differences in relative content. The material basis of TCM has restricted the modernization of TCM. Liquid chromatography-mass spectrometry (LC-MS) combines the high separation performance of chromatography and the high sensitivity of mass spectrometry. It has been widely used in the analysis of natural medicines and can greatly promote the development of TCM. Many studies have focused on the comprehensive characterization of phytochemicals, building a strategy for the rapid, accurate and systematic analysis of the chemical components of TCM through the integration of different mass spectrometric techniques, and laying the foundation for quality control and rational utilization of TCM.

Prediction of spontaneous preterm birth by cervical length changes in twin pregnancies / 中国实用妇科与产科杂志

OBJECTIVE: To investigate the predictive value of cervical length（CL）changes in spontaneous preterm birth（SPTB）in twin pregnancies in the second and third trimesters of pregnancy.METHODS: A retrospective analysis was made of 166 cases of twin pregnant women who underwent transvaginal ultrasound to measure CL during the second trimester of pregnancy（20~25 weeks）and the third trimester of pregnancy（28~32 weeks）from January 2014 to December 2017 in the Third Hospital of Peking University and Tongzhou Maternal and Child Health Hospital of Beijing.Evaluate the predictive value of CL changes in SPTB before 32 and 34 weeks.The area under the receiver-operating characteristics（ROC）curve was compared by bootstrap method.Assessment of the value of CL in the third trimester of pregnancy and CL in the second trimester of pregnancy alone in predicting SPTB before 32 and 34 weeks.RESULTS: Of the 166 cases,90 were full-term delivery and 76 were premature delivery.The median CL of mid and late pregnancy was 34 mm and 29 mm respectively,and it was 35.5 mm and 31 mm,and in full-term delivery.32.5 mm and21 mm in premature delivery,respectively.There were significant differences among the three groups（All P25 mm and CL shortening≥ 20%,it can better predict preterm birth before 32 weeks.

Identification of impurity profile in tinidazole glucose injection by UPLC-MS / 药学学报

Five components in the impurity profile of tinidazole glucose injection were detected and identified by UPLC-Q Exactive quadrupole-electrostatic field orbitrap high resolution mass spectrometry, in combination with retention time references, organic reaction mechanisms and UV spectral analysis. They are 2-methyl-5-nitroimidazole (impurity 1), 5-hydroxymethylfurfural (impurity 2), 1-(2-(ethylsulfonyl)ethyl)-2-methyl-4-nitro-1H-Imidazole (impurity 5), 1-(2-(ethylthio)ethyl)-2-methyl-5-nitro-1H-imidazole (impurity 6) and 1,4-di-N-oxo-2-methyl-5-nitro-1H-imidazole (impurity 8) respectively, of which impurities 6 and 8 are identified for the first time. These results and detection methods are useful for monitoring the manufacturing process and quality control of tinidazole and glucose injection solution.

Relationship of lymph node metastasis rate with prognosis of esophageal squamous cell carcinoma after radical resection and postoperative adjuvant chemotherapy / 中华消化外科杂志

Objective To investigate the relationship of lymph node metastasis rate (LNR) with prognosis of esophageal squamous cell carcinoma after radical resection and postoperative adjuvant chemotherapy.Methods The retrospective case-control study was conducted.The clinicopathological data of 121 patients who underwent radical resection of esophageal squamous cell carcinoma in the Peking University Cancer Hospital from January 2012 to September 2016 were collected.There were 105 males and 16 females,aged from 42 to 76 years,with a median age of 58 years.All patients underwent radical resection of esophageal cancer with at least two-field lymph nodes dissection.Some patients underwent corresponding chemotherapy and radiotherapy.The thoracic and abdominal lymph nodes were grouped according to the 7th edition standard of Americau Joint Committee on Cancer (AJCC).The lymph nodes dissected were labeled in groups,and all the lymph nodes were examined by pathology test.Observation indicators:(1) follow-up;(2) effects of LNR on prognosis of patients in different AJCC N staging;(3) relationship between LNR and postoperative adjuvant chemotherapy.Follow-up was conducted by outpatient examination,telephone interview and hospital statistical office to detect postoperative survival of patients up to February 2017.The disease-free survival time was from surgery date to date of confirmation of tumor recurrence,and the overall survival time was from surgery date to death of the patient or the last follow-up date.Measurement data with skewed distribution were expressed by M (range).The Kaplan-Meier method was used to calculate the survival rate and draw the survival curve.The Log-rank test was used for survival analysis.Results (1) Follow-up:121 patients were followed up for 3.0-94.2 months,with a median follow-up time of 27.1 months.During the follow-up,98 of 121 patients had tumor recurrence and metastasis (including 64 deaths),22 had no metastasis,and 1 had unknown tumor metastasis.The mean overall survival time of patients was 30.8 months.The 1-,3-,5-year disease-free survival rates were 47.1％,20.3％,and 5.9％,respectively.The 1-,3-,5-year overall survival rates were 93.1％,48.7％,and 35.3％,respectively.(2) Effects of LNR on prognosis of patients in different AJCC N staging:of 121 patients,46 were in N0 stage,42 were in N1 stage,28 were in N2 stage,and 5 were in N3 stage.Of 42 patients in N1 stage,35 with 0 ＜ LNR ≤ 0.15 had a disease-free survival time of 12.2 months (range,1.2-82.3 months),and 7 with LNR ＞ 0.15 had a disease-free survival time of 6.9 months (range,2.1-23.1 months);the difference between the two groups was statistically significant (x2 =3.888,P＜0.05).Of the 28 patients in N2 stage,12 with 0 ＜ LNR ≤ 0.15 had a disease-free survival time of 8.5 months (range,1.2-38.8 months),and 16 with LNR ＞ 0.15 had a disease-free survival time of 4.4 months (range,1.0-52.7 months);the difference was not statistically significant (x2 =0.007,P＞0.05).Forty-six patients in N0 stage were detected no lymph node metastasis,and only 5 cases were in N3 stage,with no analysis.(3) Relationship between LNR and postoperative adjuvant chemotherapy:of the 121 patients,56 underwent postoperative adjuvant chemotherapy,which was mainly constituted by pactitaxel,platinum,and 5-fluorouracilbased regimens,58 didn't undergo postoperative adjuvant chemotherapy,and 7 had unknown data of postoperative adjuvant chemotherapy.Of 121 patients,46 had LNR =0,47 had 0 ＜ LNR ≤ 0.15,28 had LNR ＞ 0.15.Of the 46 patients with LNR =0,17 who underwent postoperative adjuvant chemotherapy had a disease-free survival time of 8.1 months (range,3.9-66.7 months) and a overall survival time of 34.0 months (range,4.7-76.0 months);29 who didn't undergo postoperative adjuvant chemotherapy had a disease-free survival time of 18.8 months (range,1.6-53.2 months),and a overall survival time of 48.6 months (range,8.3-94.2 months);there was no significant difference in the disease-free survival time and overall survival time between the two groups (x2=0.311,0.858,P＞0.05).Of the 47 patients with 0 ＜ LNR ≤ 0.15,27 who underwent postoperative adjuvant chemotherapy had a disease-free survival time of 13.3 months (range,5.0-82.3 months),and a overall survival time of 53.1 months (range,5.7-82.3 months);20 without postoperative adjuvant chemotherapy had a disease-free survival time of 8.4 months (range,1.2-39.2 months),and a overall survival time of 26.5 months (range,5.9-52.6 months).There were significant differences in the disease-free survival time and overall survival time between the two groups (x2 =10.322,4.971,P＜0.05).Of the 28 patients with LNR ＞ 0.15 (7 had unknown data of postoperative adjuvant chemotherapy),12 who underwent adjuvant chemotherapy had a diseasefree survival time of 10.3 months (range,2.9-52.7 months),and a overall survival time of 29.5 months (range,11.2-58.5 months);9 without postoperative adjuvant chemotherapy had a disease-free survival time of 2.9 months (range,1.4-35.7 months),and a overall survival time of 14.5 months (range,3.0-62.3 months);there was a significant difference in the disease-free survival time between the two groups (x2 =6.687,P＜0.05),and no significant difference in the overall survival time between the two groups (x2=2.938,P＞ 0.05).Conclusions LNR can be used as a supplementation of AJCC N staging system.In patients with 0＜ LNR ≤ 0.15,postoperative adjuvant chemotherapy can improve disease-free survival time and overall survival time.

Optimization of response surface of fresh-cut processing technology in Corydalis Rhizoma producing area / 中草药

Objective To optimize the fresh-cutting process of Corydalis Rhizoma by response surface methodology, and obtain the best technology for fresh-cut processing of Corydalis Rhizoma. Methods The slice thickness, the hot air drying temperature and the loading amount were taken as the investigation factors. The total alkaloid content, the extract content and the drying efficiency were taken as the indicators. The weight coefficient of each index was obtained by principal component analysis method, and the comprehensive score was calculated. Single factor analysis was performed on the investigation factors to obtain the initial optimization range, and the response surface optimization method was used to optimize the final process optimization parameters. Results The best production conditions for fresh-cut processing were determined as slice thickness of 4 mm, dry load of 7 kg/m2, drying temperature of 85 ℃, total drying time of (279.0 ± 1.1) min, and comprehensive score of (0.860 6 ± 0.010 0). At this time, the total alkaloid content of Corydalis Rhizoma was (6.274 ± 0.030) mg/g, the content of the leachate was (17.86 ± 0.22)%, and the drying efficiency was (25.09 ± 0.00) g/(m2∙min). Conclusion The established drying process can better preserve the content of alkaloids and extracts in Corydalis Rhizoma, maintain high drying efficiency, ensure high quality and reduce energy consumption of enterprises, and provide a reliable theoretical basis for the production and processing of Corydalis Rhizoma pieces.

Subtypes of muscarinic acetylcholine receptors involved in the persistent activity of layer V pyramidal neurons in the primary auditory cortex of young mice / 生理学报

Cholinergic receptor activation and intracellular current injection lead to the persistent activity (PA), which may be involved in inducing neural plasticity. Our previous study showed that PA is closely related to the activation of muscarinic acetylcholine receptors (mAChRs) in pyramidal neurons of mouse primary auditory cortex (AI). However, the subtypes of mAChRs involved in PA remain unclear. Thus, using whole-cell patch-clamp recording and pharmacological methods, we investigated the role of different mAChR subtypes in inducing PA in AI layer V pyramidal neurons of young mice. The results showed that activation of mAChRs with intracellular depolarizing current induced PA in layer V pyramidal neurons. Blockade of M1, M2 or M3 subtypes prevented the PA, whereas M4 receptor antagonists did not affect the production of PA. The results suggest that the PA may be induced through a mechanism involving M1, M2 and M3 muscarinic receptors, but not M4 subtype.

Investigation on in in (), the bamboo slips of Han Dynasty in Zhangjiashan / 中国针灸

( change) in (（）, pulse change indicates the abnormal changes inside body) in the (), the Bamboo Slips of Han Dynasty in Zhangjiashan is related to the classical thought on and the theory on meridians at early era. The connotation of was explored in views of interdisciplinary perspectives, such as Chinese medicine, philology and philosophy in the ancient time. It refers to the pulse changes as mentioned in ancient medical books, indicating the abnormal changes in the body. Before the ancient medical canonization marked as sphygmology, the ancient medical scholar focused on monism. Based on the thinking mode as analogy and detecting the root from the phenomenon, it is believed that refers to the imbalance of activity inside the body, manifested with the abnormal pulse change at relevant pulse region on the body surface. Accordingly, the disorders inside the body are detected by palpation.

Role and mechanisms of hepatocyte nuclear factor 4α in bile acid induced gastric intestinal metaplasia / 中华消化杂志

Objective To investigate the roles and mechanisms of hepatocyte nuclear factor 4α (HNF4α) in chenodeoxycholic acid (CDCA) induced gastric intestinal metaplasia (IM).Methods After the immortalized gastric mucosal epithelial cells GES-1 were stimulated with CDCA at different concentration,the changes of HNF4α,caudal-related homeobox 2 (CDX2) and trefoil factor family 3 (TFF3) expressions at mRNA and protein levels in GES-1 cells and gastric cancer cell lines (AGS,SGC7901 and BGC823) were detected by real time-polymerase chain reaction (RT-PCR) and Western blotting.After GES-1 were transfected with HNF4α short hairpin RNA (shRNA) or control shRNA,and followed by CDCA stimulation,the expressions of HNF4α,CDX2 and TFF3 at protein level were determined by Western blotting.HNF4α was overexpressed in GES-1 cells and SGC7901 cells,and HNF4α was silenced in BGC823 cell line and AGS by lentiviral vector system.The expressions of HNF4α,CDX2 and TFF3 at mRNA and protein levels were tested by RT-PCR and Western blotting.Luciferase reporter assay was used to analyze the regulation role of HNF4α on CDX2.T test was performed for statistical analysis.Results The expressions of HNF4α in GES-1,SGC7901,BGC823 and AGS cells at mRNA level were 1.00 ± 0.12,263.01±10.23,848.01±18.13 and 3 049.86±91.75,respectively.The mRNAlevels of HNF4α in AGS,BGC823 and SGC7901 cells were all higher than that of GES-1 cells,and the differences were statistically significant (t=33.23,46.72 and 25.62,all P＜0.01).The expressions of HNF4α in GES-1,SGC7901,BGC823 and AGS at protein level were consistent with mRNA level.The expressions of CDX2 and TFF3 at protein level of HNF4α shRNA transfected group were lower than those of non-HNF4α shRNA transfected group.In GES-1 cells,the expressions of HNF4α,CDX2 and TFF3 of HNF4α overexpressed group at mRNA level were 16 281.839 ± 1 843.017,6.275 ± 0.137 and 17.310± 1.533,respectively;which were all higher than those of overexpressed control group (1.000 ± 0.048,1.000 ± 0.012 and 1.000±0.108,respectively),and the differences were statistically significant (t =8.83,38.29 and 10.61,all P＜0.01).In AGS cells,the expressions of HNF4α,CDX2 and TFF3 of HNF4α silenced group at mRNA level were 0.021 ± 0.001,0.088 ± 0.007 and 0.074 ± 0.002,respectively,which were lower than those of silenced control group (1.000 ± 0.108,1.000 ± 0.131 and 1.000 ± 0.122),and the differences were statistically significant (t=9.09,6.93 and 7.57,all P＜0.01).In GES-1 overexpressed cells and AGS silenced cells,the expressions of HNF4α,CDX2,TFF3 at protein level were consistent with mRNA level.In double reporter plasmid containing the CDX2 promoter CDX2 1 (-2 000～-1 bp) and CDX2-2 (-1 510～1 bp),after transfected with HNF4α shRNA,the activities were 0.387 ± 0.013 and 0.533 ± 0.040,respectively,which were lower than those of HNF4α shRNA transfected control group (0.605 ± 0.012 and 0.882 ± 0.019),and the differences were statistically significant (t =21.49 and 13.53,both P＜0.01).Conclusion HNF4α may be involved in bile acid induced intestinal metaplasia by upregulating the expression of CDX2.

The choice of demand, supply, utilization and health promotion strategy of migrant popula-tion:A perspective of behavioral model of medical service utilization / 中国卫生政策研究

With the continuous expansion of the domestic population flow,the medical and health services is-sues of migrant population are becoming more and more serious. Based on the three aspects of the demand,supply, and utilization of health services,this article explores and analyzes the utilization of health services for migrant popu-lation in Beijing in 2015 on the basis of behavioral models. The results showed that the prevalence of chronic diseases and the frequency of disease in migrant population are relatively low. The migrant population has low efficiency and overall evaluation of public health services. From the point of view of convenience and diversity of services,the sup-ply of public health services needs to be further improved. In terms of the active utilization of medical and health services,the proportion of respondents who did not participate in any medical insurance still have a large proportion, while the proportion of regular physical examination was lower. In terms of passive utilization,both outpatient and in-patients service use are low. Family income and medical insurance have influenced patients'choice of medical institu-tions to some extent. The health promotion strategy is proposed from the perspective of supply side and utilization.

Analysis on Resident Individual Financing Amount and Financing Feasibility Based on the Integration of Medical Insurance for Urban and Rural Residents in the Inner Mongolia Autonomous Region / 中国卫生经济

Objective:To calculate the individual financing amount of residents under different compensation schemes in Inner Mongolia Autonomous Region,and to analyze the feasibility of financing individual residents in the process of integration of basic medical insurance for urban and rural residents in Inner Mongolia Autonomous Region.Methods:Based on the absolute correlation model,the relative correlation model and the comprehensive correlation degree,it calculated the individual financing quota of different compensation schemes in Inner Mongolia Autonomous Region from 2011 to 2015,and analyzed the feasibility of its financing.Results:The increase in the amount of funds required for the residents in 5 years was more than 2 times,and the average annual growth rate was more than 25％.These three types of compensation programs(30％ outpatients + 70％ hospitalized).The correlation degree of the compensation scheme (40％ outpatient service + 70％ hospitalization) was between 0.60 and 0.85.The correlation degree of the compensation scheme was relatively high,which reached to 0.920.The correlation degree of these five compensation schemes was relatively low,which reached to 0.508.Conclusion:The amount of funding required for individual residents in Inner Mongolia Autonomous Region increased by years.The three types of compensation programs(30％ outpatient service + 70％ hospitalization) were more feasible than the four types of compensation programs(40％ outpatient service + 70％ hospitalization).

miR-181d Inhibits Proliferation and Promotes Apoptosis in Colon Cancer Cells / 现代检验医学杂志

Objective To detect miR-181d expression levels in colon cancer cell lines,and to study the functions of miR-181d on colon cancer cell proliferation and apoptosis.Methods RT qPCR was employed to study miR-181d cxpression levels in colon cancer cell line HCT116,HT29,LoVo,SW480 and SW620 cells,as well as in colon normal epithelial cell line HIEC.miR-181d mimic and control were transfected into LoVo cells while miR-181d inhibitor and control were transfected into SW620 cells.qRT-PCR was performed to validate the transfection efficiency.MTT assay was performed to measure cell proliferation while flow cytometry was performed to detect cell cycle and apoptosis rate.Results miR-181d was universally downregulated in all colon cancer cell lines compared to the colon normal epithelial cell line HIEC (F=29.34,P＜0.01).Overexpression of miR-181d in LoVo cells significantly decreased in vitro cell proliferation rate (F=5.403,P＜0.01).Flow cytometry indicated that cells at S phase were greatly decreased (t=4.71,P＜0.05) and apoptotic cells were gready increased compared to the control cells (t=3.47,P＜0.05).On the contrary,inhibition of miR-181d in SW620 cells significantly promoted cell proliferation (F=20.82,P＜0.01).Cell cycle was accelerated with significant increase in S phase compared to the control cells (t=2.92,P＜0.05),whereas apoptosis rano was significantly decreased (t=4.14,P＜0.05).Conclusion miR-181d was universally downregulated in colon cancer cell lines compared to the normal epithelial cell line.miR-181d inhibits cell proliferation and induces apoptosis,thus functions as an tumor suppressive miRNA.